Tumour-Agnostic Treatment

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Tumour agnostic treatment is a genomically-informed treatment strategy that enriches for novel targets regardless of histological origin. This treatment typically fulfils the following criteria [1]:

Tumours are enriched for ≥1 molecular alteration.
Alterations are likely to predict response to a therapy.
Alterations are found across a variety of cancers.

The following table summarises the key differences between development of a tumour-agnostic treatment (assessed in “basket trials”) versus traditional approval of cancer therapies [1-3].

Table 2: Tumour-Agnostic Treatment Versus Traditional Cancer Therapies

	Tumour-agnostic treatment	Traditional cancer therapies
Basis of approval	Biomarker present across many tumour types. Biomarkers of response, establishing the effects of context, and deciphering mechanisms of treatment resistance across a variety of tumour types.	Consider heterogeneity of drug effects in different biomarker-positive tumour types. Can be directed toward a specific genomic abnormality in a specific tumour type.
Patient population	Small patient cohorts with diverse tumour types and a common genomic event.	Large patient cohorts with tumours originating from a single anatomic site. Tumours that commonly have heterogeneous genomic aberrations.

In May 2017, the first approval of a tumour-agnostic treatment (pembrolizumab for tumours deficient in mismatch repair or with high microsatellite instability) was received [5]. Since then, other such approvals have followed including those for NTRK inhibitors larotrectinib and entrectinib, dorstarlimab (an anti-PD-1 antibody) and the combination of dabrafenib and trametinib in for BRAF V600E gene mutated cancers.

References

Offin M, Liu D, Drilon A. Tumor-Agnostic Drug Development. J Clin Oncol 2018; 286-295.
Remon J, Dienstmann R. Precision oncology: separating the wheat from the chaff. ESMO Open 2018; 3: e000446.
Flaherty KT, Le DT, Lemery S. Tissue-Agnostic Drug Development. Am Soc Clin Oncol Educ Book 2017; 38: 222-230.
Looney AM, Nawaz K, Webster RM. Tumour-agnostic therapies. Nat Rev Drug Discov. 2020 Jun;19(6):383-384.
Davis AA, McKee AE, Kibbe WA, Villaflor VM. Complexity of Delivering Precision Medicine: Opportunities and Challenges. Am Soc Clin Oncol Educ Book 2018; 38: 998-1007.